Induction of innate immunity and its perturbation by influenza viruses

Protein & Cell, Jul 2015

Influenza A viruses (IAV) are highly contagious pathogens causing dreadful losses to human and animal, around the globe. IAVs first interact with the host through epithelial cells, and the viral RNA containing a 5′-triphosphate group is thought to be the critical trigger for activation of effective innate immunity via pattern recognition receptors-dependent signaling pathways. These induced immune responses establish the antiviral state of the host for effective suppression of viral replication and enhancing viral clearance. However, IAVs have evolved a variety of mechanisms by which they can invade host cells, circumvent the host immune responses, and use the machineries of host cells to synthesize and transport their own components, which help them to establish a successful infection and replication. In this review, we will highlight the molecular mechanisms of how IAV infection stimulates the host innate immune system and strategies by which IAV evades host responses.

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Induction of innate immunity and its perturbation by influenza viruses

© The Author(s) 2015. This article is published with open access at Springerlink.com and journal.hep.com.cn Induction of innate immunity and its perturbation by influenza viruses Mohsan Ullah Goraya 2 3 Song Wang 2 3 Muhammad Munir 1 2 Ji-Long Chen 0 2 3 0 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China Received June 6, 2015 Accepted June 29, 2015 1 The Pirbright Institute , Ash Road, Pirbright, Woking GU24 0NF , UK 2 influenza A virus , innate immunity, immune 3 College of Animal Science, Fujian Agriculture and Forestry University , Fuzhou 350002 , China Influenza A viruses (IAV) are highly contagious pathogens causing dreadful losses to human and animal, around the globe. IAVs first interact with the host through epithelial cells, and the viral RNA containing a 5′-triphosphate group is thought to be the critical trigger for activation of effective innate immunity via pattern recognition receptors-dependent signaling pathways. These induced immune responses establish the antiviral state of the host for effective suppression of viral replication and enhancing viral clearance. However, IAVs have evolved a variety of mechanisms by which they can invade host cells, circumvent the host immune responses, and use the machineries of host cells to synthesize and transport their own components, which help them to establish a successful infection and replication. In this review, we will highlight the molecular mechanisms of how IAV infection stimulates the host innate immune system and strategies by which IAV evades host responses. escape - Influenza A viruses (IAV) cause highly pathogenic respiratory problems in human and animals. It is the major cause of annual epidemics and occasional pandemics in humans, responsible for 3–5 million cases of severe clinical infections and 250,000 to 500,000 fatal cases every year throughout the world (Stohr, 2002). Infection with influenza virus varies from subclinical infection of upper respiratory tract to lethal infection of lower respiratory system. Due to differences in pathogenesis of various influenza viruses, biology of the disease is not fully understood. Influenza virus infection induces host innate immune responses, which results in the termination of virus replication. On the other hand, IAV has evolved multiple strategies to circumvent the host innate immunity to establish a successful infection and replication. In addition to typical seasonal infections, IAV can also undergo substantial changes (recombination/antigenic shift) that leave imprints of infection with little to no protective immunity and uplift mortality rate even among healthy young adults infected with IAV (Horimoto and Kawaoka, 2001; Palese, 2004). Only, the last century we have observed three major pandemics: the 1918 Spanish flu, 1957 Asian flu, and the 1968 Hong Kong flu; with the 1918 pandemic being the most concerning and significant, causing an estimated 30–50 million deaths worldwide (Horimoto and Kawaoka, 2001, 2005). Furthermore, the recent appearance of IAV strains with pandemic potential, such as H1N1 “swine flu” and H5N1 avian influenza, have highlighted the importance of studies about IAV infections and the innate and adaptive immune responses that control and eliminate infection. Thus, this review will focus on discussion of host innate immune responses to IAV infection and viral escape from the innate sensing. BIOLOGY AND STRUCTURE OF IAV Influenza viruses are categorized in the family of Orthomyxoviridae. The virus particle is enveloped and contains a segmented, single-stranded, negative sense RNA genome (Klenk et al., 2004). Its genome possesses eight segments encoding 13 proteins (Jagger et al., 2012), out of which 8 are considered core proteins whereas the rest are called accessory proteins. Additionally, a putative open reading frame (ORF) in the positive-sense of segment 8 has been identified, which encodes for a hypothetical negative sense protein (NSP) of ∼25 kDa (Zhirnov et al., 2007). However, the role of NSP still remains elusive. Another protein encoded within segment 2 (in addition to PB1 and PB1-F2) has been identified, termed N40 (Wise et al., 2009). Morphologically, the viral particles are creased with a lipid bilayer, which is derived from the host plasma membrane. The lipid bilayer contains almost 500 spikes (each of 10–14 nm), of viral proteins hemagglutinin (HA) and neuraminidase (NA), protruded out from the envelope. These spikes appear as either rod-shaped (HA) or mushroom shaped (NA). The ratio of HA to NA generally varies from 4:1 to 5:1. The high density of HA is probable to enhance the chances for viral attachment. Additionally, matrix protein 2 (M2) is also enriched into the lipid envelope. The ratio between M2 and HA is usually about 1:10 to 1:100 (Zebedee and Lamb, 1988). Envelope viral glycoproteins (HA and NA) have stumpy kinesis within envelope. These two (...truncated)


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Mohsan Ullah Goraya, Song Wang, Muhammad Munir, Ji-Long Chen. Induction of innate immunity and its perturbation by influenza viruses, Protein & Cell, 2015, pp. 712-721, Volume 6, Issue 10, DOI: 10.1007/s13238-015-0191-z